The incidence rate and influence factors of hemolysis, lipemia, icterus in fasting serum biochemistry specimens.

OBJECTIVE: Hemolysis, icterus, and lipemia (HIL) of blood samples have been a concern in hospitals because they reflect pre-analytical processes' quality control. However, very few studies investigate the influence of patients' gender, age, and department, as well as sample-related turnaround time, on the incidence rate of HIL in fasting serum biochemistry specimens. METHODS: A retrospective, descriptive study was conducted to investigate the incidence rate of HIL based on the HIL index in 501,612 fasting serum biochemistry specimens from January 2017 to May 2018 in a tertiary university hospital with 4,200 beds in Sichuan, southwest China. A subgroup analysis was conducted to evaluate the differences in the HIL incidence rate by gender, age and department of patients, and turnaround time of specimens. RESULTS: The incidence rate of hemolysis, lipemia and icterus was 384, 53, and 612 per 10,000 specimens. The male patients had a significantly elevated incidence of hemolysis (4.13% vs. 3.54%), lipemia (0.67% vs. 0.38%), and icterus (6.95% vs. 5.43%) than female patients. Hemolysis, lipemia, and icterus incidence rate were significantly associated with the male sex with an odds ratio (OR) of 1.174 [95% confidence interval (CI), 1.140-1.208], 1.757 (95%CI: 1.623-1.903), and 1.303 (95%CI: 1.273-1.333), respectively, (P<0.05). The hospitalized patients had a higher incidence of hemolysis (4.03% vs. 3.54%), lipemia (0.63% vs. 0.36%), and icterus (7.10% vs. 4.75%) than outpatients (P<0.001). Specimens with relatively longer transfer time and/or detection time had a higher HIL incidence (P<0.001). The Pediatrics had the highest incidence of hemolysis (16.2%) with an adjusted OR (AOR) of 4.93 (95%CI, 4.59-5.29, P<0.001). The Neonatology department had the highest icterus incidence (30.1%) with an AOR of 4.93 (95%CI: 4.59-5.29, P<0.001). The Neonatology department (2.32%) and Gastrointestinal Surgery (2.05%) had the highest lipemia incidence, with an AOR of 1.17 (95%CI: 0.91-1.51) and 4.76 (95%CI: 4.70-5.53), both P-value <0.001. There was an increasing tendency of hemolysis and icterus incidence for children under one year or adults aged more than 40. CONCLUSION: Evaluation of HIL incidence rate and HIL-related influence factors in fasting serum biochemistry specimens are impartment to interpret the results more accurately and provide better clinical services to patients.

Extracellular vesicle release and uptake by the liver under normo- and hyperlipidemia.

Liver plays a central role in elimination of circulating extracellular vesicles (EVs), and it also significantly contributes to EV release. However, the involvement of the different liver cell populations remains unknown. Here, we investigated EV uptake and release both in normolipemia and hyperlipidemia. C57BL/6 mice were kept on high fat diet for 20-30 weeks before circulating EV profiles were determined. In addition, control mice were intravenously injected with 99mTc-HYNIC-Duramycin labeled EVs, and an hour later, biodistribution was analyzed by SPECT/CT. In vitro, isolated liver cell types were tested for EV release and uptake with/without prior fatty acid treatment. We detected an elevated circulating EV number after the high fat diet. To clarify the differential involvement of liver cell types, we carried out in vitro experiments. We found an increased release of EVs by primary hepatocytes at concentrations of fatty acids comparable to what is characteristic for hyperlipidemia. When investigating EV biodistribution with 99mTc-labeled EVs, we detected EV accumulation primarily in the liver upon intravenous injection of mice with medium (326.3 ± 19.8 nm) and small EVs (130.5 ± 5.8 nm). In vitro, we found that medium and small EVs were preferentially taken up by Kupffer cells, and liver sinusoidal endothelial cells, respectively. Finally, we demonstrated that in hyperlipidemia, there was a decreased EV uptake both by Kupffer cells and liver sinusoidal endothelial cells. Our data suggest that hyperlipidema increases the release and reduces the uptake of EVs by liver cells. We also provide evidence for a size-dependent differential EV uptake by the different cell types of the liver. The EV radiolabeling protocol using 99mTc-Duramycin may provide a fast and simple labeling approach for SPECT/CT imaging of EVs biodistribution.

Immunomodulation of IL-33 and IL-37 with Vitamin D in the Neointima of Coronary Artery: A Comparative Study between Balloon Angioplasty and Stent in Hyperlipidemic Microswine.

Inflammation is a major contributor to the development and progression of atherosclerosis. Interleukin (IL)-33 and IL-37, members of the IL-1 family, modulate inflammation, with IL-33 having a pro-inflammatory effect and IL-37 having anti-inflammatory properties. IL-37 is constitutively expressed at low levels but upregulated in inflammatory contexts. The aim of this study was to evaluate the effect of vitamin D on the expression of IL-33, IL-37, macrophages, and caspase-1 in the neointimal tissue of coronary artery in Yucatan microswine with vitamin D deficient, sufficient, and supplemented status. The intimal injury was induced by balloon angioplasty and stenting in the coronary artery, and tissues were harvested after 6 months. The expression of various proteins of interest was evaluated by immunostaining. Increased expression of IL-33 and IL-37 in the neointimal tissue of the vitamin D deficient, as compared to the sufficient and supplemented microswine, as revealed by histological evaluation and semi-quantitative analysis, suggested the immunomodulatory effect of vitamin D on the expression of IL-33 and IL-37. The minimal expression or absence of IL-33 and IL-37 expression in stented arteries is suggestive of an attenuated inflammatory response in stented arteries, compared to balloon angioplasty. The decreased IL-33 expression in the sufficient and supplemented microswine could be a potential mechanism for controlling the inflammatory process and neointima formation leading to attenuated luminal narrowing of the coronary artery. Overall, these results support supplementation of vitamin D to attenuate inflammation, neointima formation, and restenosis.

ILF3 is responsible for hyperlipidemia-induced arteriosclerotic calcification by mediating BMP2 and STAT1 transcription.

Calcification is common in atherosclerotic plaque and can induce vulnerability, which further leads to myocardial infarction, plaque rupture and stroke. The mechanisms of atherosclerotic calcification are poorly characterized. Interleukin enhancer binding factor 3 (ILF3) has been identified as a novel factor affecting dyslipidemia and stroke subtypes. However, the precise role of ILF3 in atherosclerotic calcification remains unclear. In this study, we used smooth muscle-conditional ILF3 knockout (ILF3SM-KO) and transgenic mice (ILF3SM-Tg) and macrophage-conditional ILF3 knockout (ILF3M-KO) and transgenic (ILF3M-Tg) mice respectively. Here we showed that ILF3 expression is increased in calcified human aortic vascular smooth muscle cells (HAVSMCs) and calcified atherosclerotic plaque in humans and mice. We then found that hyperlipidemia increases ILF3 expression and exacerbates calcification of VSMCs and macrophages by regulating bone morphogenetic protein 2 (BMP2) and signal transducer and activator of transcription 1 (STAT1) transcription. We further explored the molecular mechanisms of ILF3 in atherosclerotic calcification and revealed that ILF3 acts on the promoter regions of BMP2 and STAT1 and mediates BMP2 upregulation and STAT1 downregulation, which promotes atherosclerotic calcification. Our results demonstrate the effect of ILF3 in atherosclerotic calcification. Inhibition of ILF3 may be a useful therapy for preventing and even reversing atherosclerotic calcification.

Hyperlipidemic Conditions Impact Force-Induced Inflammatory Response of Human Periodontal Ligament Fibroblasts Concomitantly Challenged with P. gingivalis-LPS.

In obese patients, enhanced serum levels of free fatty acids (FFA), such as palmitate (PA) or oleate (OA), are associated with an increase in systemic inflammatory markers. Bacterial infection during periodontal disease also promotes local and systemic low-grade inflammation. How both conditions concomitantly impact tooth movement is largely unknown. Thus, the aim of this study was to address the changes in cytokine expression and the secretion of human periodontal ligament fibroblasts (HPdLF) due to hyperlipidemic conditions, when additionally stressed by bacterial and mechanical stimuli. To investigate the impact of obesity-related hyperlipidemic FFA levels on HPdLF, cells were treated with 200 µM PA or OA prior to the application of 2 g/cm2 compressive force. To further determine the additive impact of bacterial infection, HPdLF were stimulated with lipopolysaccharides (LPS) obtained from Porphyromonas gingivalis. In mechanically compressed HPdLF, PA enhanced COX2 expression and PGE2 secretion. When mechanically stressed HPdLF were additionally stimulated with LPS, the PGE2 and IL6 secretion, as well as monocyte adhesion, were further increased in PA-treated cultures. Our data emphasize that a hyperlipidemic condition enhances the susceptibility of HPdLF to an excessive inflammatory response to compressive forces, when cells are concomitantly exposed to bacterial components.

The Metaflammatory and Immunometabolic Role of Macrophages and Microglia in Diabetic Retinopathy.

Emergent studies reveal the roles of inflammatory cells and cytokines in the development of diabetic retinopathy (DR), which is gradually portrayed as a chronic inflammatory disease accompanied by metabolic disorder. Through the pathogenesis of DR, macrophages or microglia play a critical role in the inflammation, neovascularization, and neurodegeneration of the retina. Conventionally, macrophages are generally divided into M1 and M2 phenotypes which mainly rely on glycolysis and oxidative phosphorylation, respectively. Recently, studies have found that nutrients (including glucose and lipids) and metabolites (such as lactate), can not only provide energy for cells, but also act as signaling molecules to regulate the function and fate of cells. In this review, we discussed the intrinsic correlations among the metabolic status, polarization, and function of macrophage/microglia in DR. Hyperglycemia and hyperlipidemia could induce M1-like and M2-like macrophages polarization in different phases of DR. Targeting the regulation of microglial metabolic profile might be a promising therapeutic strategy to modulate the polarization and function of macrophages/microglia, thus attenuating the progression of DR.

Male and Female Animals Respond Differently to High-Fat Diet and Regular Exercise Training in a Mouse Model of Hyperlipidemia.

Inappropriate nutrition and a sedentary lifestyle can lead to obesity, one of the most common risk factors for several chronic diseases. Although regular physical exercise is an efficient approach to improve cardiometabolic health, the exact cellular processes are still not fully understood. We aimed to analyze the morphological, gene expression, and lipidomic patterns in the liver and adipose tissues in response to regular exercise. Healthy (wild type on a normal diet) and hyperlipidemic, high-fat diet-fed (HFD-fed) apolipoprotein B-100 (APOB-100)-overexpressing mice were trained by treadmill running for 7 months. The serum concentrations of triglyceride and tumor necrosis factor α (TNFα), as well as the level of lipid accumulation in the liver, were significantly higher in HFD-fed APOB-100 males compared to females. However, regular exercise almost completely abolished lipid accumulation in the liver of hyperlipidemic animals. The expression level of the thermogenesis marker, uncoupling protein-1 (Ucp1), was significantly higher in the subcutaneous white adipose tissue of healthy females, as well as in the brown adipose tissue of HFD-fed APOB-100 females, compared to males. Lipidomic analyses revealed that hyperlipidemia essentially remodeled the lipidome of brown adipose tissue, affecting both the membrane and storage lipid fractions, which was partially restored by exercise in both sexes. Our results revealed more severe metabolic disturbances in HFD-fed APOB-100 males compared to females. However, exercise efficiently reduced the body weight, serum triglyceride levels, expression of pro-inflammatory factors, and hepatic lipid accumulation in our model.

Postprandial lipemia causes oxidative stress in dogs.

Oxidative stress (OS) has been strongly associated with postprandial lipemia (PPL) in humans, and still requires further investigation in dogs. However, since lipemia interferes with spectrophotometric determinations such as those used to assess OS, the present study investigated the effect of PPL on OS parameters of healthy dogs. Twenty dogs had lipemic postprandial samples compared to the average of two non-lipemic moments. Subsequently, PPL was simulated in vitro using a commercial lipid emulsion and twelve pools of non-lipemic serum of these dogs were used to simulate the minimum, median and maximum concentrations of triglycerides obtained during the lipemic state. Serum OS parameters were assessed using the antioxidants uric acid, albumin and total bilirubin; total antioxidant capacity (TAC); total oxidant capacity (TOC); and lipid peroxidation. In vivo PPL caused an increase in albumin, TAC-CUPRAC, TAC-FRAP, uric acid (p < 0.0001), TOC (p = 0.0012) and total bilirubin (p = 0.0245); reduction of TAC-ABTS (p = 0.0008); and did not alter the lipid peroxidation (p = 0.8983). In vitro, levels of albumin increased at the three lipemic concentrations (p < 0.0001), uric acid increased in the median and maximum levels (p < 0.0001), and total bilirubin concentration increased only at the maximum lipemic level (p = 0.0012). All lipemic levels tested increased TAC-ABTS (p = 0.0011) and TAC-FRAP (p < 0.0001). TAC-CUPRAC (p = 0.5002), TOC (p = 0.5938) and lipid peroxidation (p = 0.4235) were not affected by in vitro lipemia. In conclusion, both the in vivo postprandial state and in vitro simulated lipemia affect oxidative stress markers in dogs depending on the oxidative stress marker, and thus the postprandial state and/or lipemic samples should be avoided.

Patient Characteristics and Treatment Patterns among Medicare Beneficiaries Initiating PCSK9 Inhibitor Therapy.

PURPOSE: There is limited real-world evidence around use of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) among US older adults. This study examined baseline characteristics of fee-for-service (FFS) Medicare beneficiaries newly initiating PCSK9i therapy during the period immediately following market availability. METHODS: This cross-sectional study used Medicare claims (2013-2016) to identify 5051 FFS Medicare beneficiaries who filled ≥ 1 PCSK9i prescription between August 2015 and December 2016. We analyzed patient demographics, clinical characteristics, and baseline healthcare expenditures in the 12-month period prior to PCSK9i initiation, for these beneficiaries. RESULTS: Most beneficiaries initiating PCSK9i were female (57%), < 75 years of age (61%), white (89%), and lived in metropolitan areas (83%). At baseline, these PCSK9i initiators had 6 chronic conditions on average, with conditions such as hyperlipidemia, hypertension, and ischemic heart disease being most prevalent. Approximately 88% had a diagnosis of atherosclerotic cardiovascular disease (ASCVD), and 14% experienced acute cardiovascular events during the 12-month baseline period. Use of any statin and/or ezetimibe ranged from 54 to 76% in the 6-month and 24-month baseline period. Their total annual Medicare expenditures averaged US$17,552, of which most were attributable to ambulatory care and prescription use, in the 12-month baseline period. CONCLUSION: High burden of cardiovascular conditions and prescription expenditures at baseline were common among FFS beneficiaries initiating PCSK9i therapy. These findings suggest that physicians prescribe PCSK9i to elderly patients at high risk for adverse cardiovascular events. Considering the evolving treatment landscape, PCSK9i utilization might increase in Medicare.

Muscular strength and cardiovascular risk factors in adults: a systematic review.

OBJECTIVE: The purpose of this study was to identify and summarize the relationships between MS and individual components of metabolic syndrome (MetS) [high waist circumference (WC), high blood pressure (BP), high systolic blood pressure (SBP), high diastolic blood pressure (DBP), high triglycerides (TG), fasting blood glucose (GL) and low HDL cholesterol levels (HDL-C)] in adults. METHODS: A systematic review was performed on six electronic databases (Lilacs, Pubmed, Scielo, Scopus, Sportdiscus, and Web of Knowledge), with complimentary searches in reference lists. The databases were investigated without restrictions regarding the period of publication. RESULTS: Of the 6,833 articles initially identified, 17 were included, with data on 43,343 adults. Higher MS values were associated with lower WC values. Different results in relation to the association between MS and BP, MS and SBP, and MS and DBP were verified. In addition, inconclusive results were verified in the relationship between MS and TG, MS and HDL-C, and MS and GL. CONCLUSION: Higher MS values were related with lower WC in adults. More evidence from longitudinal studies with high methodological rigor is needed to elucidate the relationship between MS and CVD among adults.

Lipotoxicity-associated inflammation is prevented by guarana (Paullinia cupana) in a model of hyperlipidemia.

Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.

Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.

SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3. Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. Furthermore, we determined that SQSTM1 captured SCAP after its exit from the ER. The interaction of SCAP and SQSTM1 requires the WD40 domain of SCAP and the TB domain of SQSTM1. Interestingly, lycorine triggers the lysosome translocation of SCAP independent of autophagy. We termed this novel protein degradation pathway as the SQSTM1-mediated autophagy-independent lysosomal degradation (SMAILD) pathway. In vivo, lycorine ameliorates high-fat diet-induced hyperlipidemia, hepatic steatosis, and insulin resistance in mice. Our study demonstrated that the inhibition of SCAP through the SMAILD pathway could be employed as a useful therapeutic strategy for treating metabolic diseases.Abbreviation: 25-OHD: 25-hydroxyvitamin D; 3-MA: 3-methyladenine; ABCG5: ATP binding cassette subfamily G member 5; ABCG8: ATP binding cassette subfamily G member 8; ACACA: acetyl-CoA carboxylase alpha; AEBSF: 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride; AHI: anhydroicaritin; AKT/protein kinase B: AKT serine/threonine kinase; APOE: apolipoprotein E; ATF6: activating transcription factor 6; ATG: autophagy-related; BAT: brown adipose tissue; CD274/PD-L1: CD274 molecule; CETSA: cellular thermal shift assay; CMA: chaperone-mediated autophagy; COPII: cytoplasmic coat protein complex-II; CQ: chloroquine; DDIT3/CHOP: DNA damage inducible transcript 3; DNL: de novo lipogenesis; EE: energy expenditure; EGFR: epithelial growth factor receptor; eMI: endosomal microautophagy; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FADS2: fatty acid desaturase 2; FASN: fatty acid synthase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvate transaminase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCS1: 3-hydroxy-3-methylglutaryl-CoA synthase 1; HSP90B1/GRP94: heat shock protein 90 beta family member 1; HSPA5/GRP78: heat hock protein family A (Hsp70) member 5; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INSIG1: insulin induced gene 1; LAMP2A: lysosomal associated membrane protein 2A; LDLR: low density lipoprotein receptor; LyTACs: lysosome targeting chimeras; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MBTPS1: membrane bound transcription factor peptidase, site 1; MEF: mouse embryonic fibroblast; MST: microscale thermophoresis; MTOR: mechanistic target of rapamycin kinase; MVK: mevalonate kinase; PROTAC: proteolysis targeting chimera; RQ: respiratory quotient; SCAP: SREBF chaperone; SCD1: stearoyl-coenzemy A desaturase 1; SMAILD: sequestosome 1 mediated autophagy-independent lysosomal degradation; SQSTM1: sequestosome 1; SREBF: sterol regulatory element binding transcription factor; TNFRSF10B/DR5: TNF receptor superfamily member 10b; TRAF6: TNF receptor associated factor 6; UPR: unfolded protein response; WAT: white adipose tissue; XBP1: X-box binding protein 1.

Concepts and Controversies: Lipid Management in Patients with Chronic Kidney Disease.

Atherosclerotic cardiovascular disease (ASCVD) remains an important contributor of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is recognized as an important risk enhancer that identifies patients as candidates for more intensive low-density lipoprotein (LDL) cholesterol lowering. However, there is controversy regarding the efficacy of lipid-lowering therapy, especially in patients on dialysis. Among patients with CKD, not yet on dialysis, there is clinical trial evidence for the use of statins with or without ezetimibe to reduce ASCVD events. Newer cholesterol lowering agents have been introduced for the management of hyperlipidemia to reduce ASCVD, but these therapies have not been tested in the CKD population except in secondary analyses of patients with primarily CKD stage 3. This review summarizes the role of hyperlipidemia in ASCVD and treatment strategies for hyperlipidemia in the CKD population.

Cardiometabolic Syndrome: An Update on Available Mouse Models.

Cardiometabolic syndrome (CMS), a disease entity characterized by abdominal obesity, insulin resistance (IR), hypertension, and hyperlipidemia, is a global epidemic with approximately 25% prevalence in adults globally. CMS is associated with increased risk for cardiovascular disease (CVD) and development of diabetes. Due to its multifactorial etiology, the development of several animal models to simulate CMS has contributed significantly to the elucidation of the disease pathophysiology and the design of therapies. In this review we aimed to present the most common mouse models used in the research of CMS. We found that CMS can be induced either by genetic manipulation, leading to dyslipidemia, lipodystrophy, obesity and IR, or obesity and hypertension, or by administration of specific diets and drugs. In the last decade, the ob/ob and db/db mice were the most common obesity and IR models, whereas Ldlr-/- and Apoe-/- were widely used to induce hyperlipidemia. These mice have been used either as a single transgenic or combined with a different background with or without diet treatment. High-fat diet with modifications is the preferred protocol, generally leading to increased body weight, hyperlipidemia, and IR. A plethora of genetically engineered mouse models, diets, drugs, or synthetic compounds that are available have advanced the understanding of CMS. However, each researcher should carefully select the most appropriate model and validate its consistency. It is important to consider the differences between strains of the same animal species, different animals, and most importantly differences to human when translating results.

Omega-3 polyunsaturated fatty acids: anti-inflammatory and anti-hypertriglyceridemia mechanisms in cardiovascular disease.

Cardiovascular disease (CVD) is the world's most recognized and notorious cause of death. It is known that increased triglyceride-rich lipoproteins (TRLs) and remnants of triglyceride-rich lipoproteins (RLP) are the major risk factor for CVD. Furthermore, hypertriglyceridemia commonly leads to a reduction in HDL and an increase in atherogenic small dense low-density lipoprotein (sdLDL or LDL-III) levels. Thus, the evidence shows that Ω-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have a beneficial effect on CVD through reprogramming of TRL metabolism, reducing inflammatory mediators (cytokines and leukotrienes), and modulation of cell adhesion molecules. Therefore, the purpose of this review is to provide the molecular mechanism related to the beneficial effect of Ω-3 PUFA on the lowering of plasma TAG levels and other atherogenic lipoproteins. Taking this into account, this study also provides the TRL lowering and anti-inflammatory mechanism of Ω-3 PUFA metabolites such as RvE1 and RvD2 as a cardioprotective function.

Drp1-mediated mitochondrial fission is involved in oxidized low-density lipoprotein-induced AF cella poptosis.

This study aimed to assess the negative effect of oxidized low-density lipoprotein (oxLDL) on annulus fibrosus (AF) cells and decipher the mechanism of action of the process. After treating AF cells with various concentrations (0, 25, 50, 100, and 200 µg/mL) of oxLDL for 24 and 48 hours, their viability was evaluated using cell counting kit-8 and live/dead staining. The percentage of AF cell death was determined with Annexin V/propidium iodide apoptosis staining. The expression of proteins related to the mitochondrial apoptosis pathway was determined using Western blot. Additionally, mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were assessed with JC-1 staining and dichlorodihydrofluorescein diacetate ormitoSOX probes, respectively. Mitochondrial morphology was observed with a transmission electron microscope. After treatment with oxLDL, AF cell viability decreased, pro-apoptosis proteins (such as Bax, cleaved caspase-9, and cleaved caspase-3) increased, and anti-apoptosis proteins (Bcl-2) declined. Excessive ROS and diminished MMP were also detected during this process, as were enhanced mitochondrial fission and augmented Drp1 expression. Furthermore, knocking down the expression of Drp1 rescued oxLDL-induced AF cell death. Collectively, these results suggest that oxLDL induces AF cell death through a mitochondria-related pathway. Enhanced mitochondrial fission was involved in oxLDL-induced AF cell death. Targeting Drp1, a target for regulating the process of mitochondrial fission, may be a feasible strategy for preventing intervertebral disc degeneration in hyperlipidemia.

The Relationship of Functional Status of Cortisol, Testosterone, and Parameters of Metabolic Syndrome in Male Schizophrenics.

BACKGROUND: The cross-sectional study is aimed at investigating the relationship between cortisol, testosterone, and metabolic characteristics among male schizophrenics. METHODS: 174 patients were grouped based on their risk of metabolic syndrome (MetS) into the non-MetS, high-risk-MetS (HR-MetS), or MetS groups. Metabolic indices (body mass index (BMI), mean arterial pressure (MAP), cholesterol, triglyceride, and fasting blood glucose (FBG)) were associated with cortisol and testosterone levels using correlation analysis. Multiple linear regression analysis was used to associate the correlations between the WHO Quality of Life-BREF (WHOQOL-BREF) score and the five metabolic indices. RESULTS: The WHOQOL-BREF score for the non-MetS group significantly differed from the scores of the HR-MetS and MetS groups. The triglyceride level was positively correlated with the cortisol level, while all five metabolic indices were negatively correlated with testosterone level. Stepwise regression analysis produced a model predicting WHOQOL-BREF scores with four variables including MAP, intelligence quotient (IQ), FBG, and age. The correlation analysis then showed that there was a weak linear correlation between the testosterone level and all five metabolic indices. CONCLUSIONS: Among the five metabolic indices, the risks of hypertension and hyperglycemia are correlated with the quality of life in male schizophrenics rather than those of obesity or hyperlipidemia.

Interactive associations of sex and hyperlipidemia with calcific tendinitis of the shoulder in Taiwanese adults.

Calcific tendinitis (CT) of the shoulder is a painful disorder usually identified in individuals aged 40 and 60 years. The estimated global prevalence of CT is 2.7% to 36%. We examined the association of hyperlipidemia and sex with CT of the shoulder using Taiwan Biobank (TWB) and the National Health Insurance Research Database (NHIRD).Data were available for 9903 TWB participants who were recruited between 2008 and 2015. We used multiple logistic regression analysis to estimate the odds ratios (OR) and 95% confidence intervals (CI) for CT of the shoulder.Overall, 1564 women, and 1491 men were identified with hyperlipidemia. Women, compared to men, had higher odds of CT of the shoulder (OR, 1.53; 95% CI, 1.08-2.16). Hyperlipidemia, compared to no hyperlipidemia, was associated with an increased risk of CT (OR, 1.40; 95% CI, 1.02-1.93). The test for interaction was significant for sex and hyperlipidemia (P = .006). After stratification, the odds ratio for CT was 1.95 (95% CI, 1.30-2.92) in women and 0.82 (95% CI, 0.48-1.39) in men, respectively. Compared to men with no hyperlipidemia, the odds ratio was 0.86 (95% CI, 0.53-1.38) for men with hyperlipidemia and 2.00 (95% CI, 1.29-3.10) for women with hyperlipidemia.Importantly, our findings indicated that the risk for CT of the shoulder was higher among Taiwanese women with hyperlipidemia. However, CT risk among their male counterparts with hyperlipidemia was not significant.

Coronary CTA to Investigate Predictive Value of Left Atrial Appendage for Cardiogenic Stroke in Patients with Nonvalvular Atrial Fibrillation.

PURPOSE: To investigate the predictive value of changes in LAA size and function for cardiogenic stroke (CS) in patients with NVAF by coronary CTA examination. Materials and Method. 179 patients with NVAF were selected and grouped according to the outbreak of acute ischemic stroke and TIA within 2 years after coronary CTA examination. Those who met the criteria for CS were selected as cases (87 patients), and those neither stroke nor TIA as controls (92 patients). LAA size of selected patients was measured and data postprocessing was performed. The differences of baseline data and LAA parameters between groups were analyzed. The impacts of BMI, hyperlipidemia, the duration of AF, the LAAOA Index, and the LAAEF on CS were assessed by binary logistic regression. The predictive abilities of LAAOA Index, LAAEF, and the combined predictor were assessed by ROC curves. RESULTS: Proportions of BMI ≥ 25, prevalence of hyperlipidemia, duration of AF, and LAAODmax, LAAODmin, LAAOA, LAAVmax, and LAAVmin with their correction index were greater in cases than controls. The LAAEF was lower in cases than that in controls. The binary logistic regression model showed an increase in LAAOA Index (P = 0.005) and a decrease in LAAEF (P < 0.001) were independent risk factors for CS. ROC curve analysis showed that the optimal cutoff values of LAAOA Index and LAAEF to predict CS were 3.16 cm2/m2 and 38.71%, with AUC value of 0.712 and 0.734, respectively. The LAAOA Index-LAAEF combined predictor (AUC value = 0.786) was likely superior to either LAAOA Index or LAAEF. CONCLUSIONS: Coronary CTA can provide additional valuable parameters, as a by-product of coronary artery assessment without additional radiation dose, for the risk assessment of CS in patients with NVAF. Coronary CTA may make up for the limitation of single indicator of CHA2DS2-VASc in guiding anticoagulation program, to reduce the incidence of embolism and bleeding events.